Post on 20-Aug-2020
Discussão de casos
HNSCC
ECIP 2018
Gilberto de Castro JuniorProfessor Colaborador Livre-Docente – Faculdade de Medicina
da USP
Serviço de Oncologia Clínica - Instituto do Câncer do Estado de
São Paulo
Centro de Oncologia - Hospital Sírio Libanês
Risco em CECCP
Tratamento adjuvante
Tratamento adjuvante
CECCP
Tratamento adjuvante CECCP
RTOG 95-01EORTC 22931
Tratamento adjuvante
do CECCP
Bernier et al. Head Neck 2005
Tratamento adjuvante
do CECCP
Bernier et al. Head Neck 2005
Pignon et al.,
2009
MACH-NC 2009
Pignon et al.,
2009
MACH-NC 2009
MACH-NC 2009
Pignon et al. Radiother Oncol
2009
Pignon et al.,
2009
MACH-NC 2009
Mucosite Dermatite
Candidíase
Toxicidade aguda
Graus 1 ou 2 Graus 3 ou 4
n (%) n (%)
Mucosite 14 (47) 12 (40)
Dermatite 19 (63) 7 (23)
Disfagia 9 (30) 14 (47)
Náuseas 14 (47) 4 (13)
Vômitos 17 (57) 3 (10)
Infecção 11 (37) 4 (13)
Anemia 15 (50) 7 (23)
Leucopenia 4 (13) 5 (16)
Linfopenia 12 (40) 7 (23)
Castro G Jr. et al. Eur Arch Otorhinolaryngol
2007;264:1475-82
Toxicidade aguda CCR
Bonner trial
R.R
.A.
9%
NNT = 11,1
SO
5 a
nos
36,4 x 45,6%
H.R
.
0,71
P = 0,018
Bonner trial
Bonner trial
RTOG 0522: Stage III-IV
Phase III Trial
Stage III and IVa SCC of:
– Oropharynx
– Hypopharynx
– Larynx
Stratify:
– Larynx vs. others
– N0~N1,2a,2b~N2c-3
– KPS
60–80 ~ 90–100
– 3-D vs IMRTb
1.Accelerated FXb +
CDDP: 100 mg/m2, q3W X 2
2.
Accelerated FXb +
CDDP: 100 mg/m2, q3W X 2
aExclude T1 any N and T2N1; b3-D: AFX-CB (72 Gy/42 F/6 W) IMRT: 70 Gy/35 F/6W (BID x 5d)
Cetuximab:
400 mg/m2, Week –1
250 mg/m2/w, Wks 2–8
R
A
N
D
O
M
I
Z
E
n=720
Qual o papel da
QT neoadj no
HNSCC ?• Avaliar resposta tumoral in vivo
• Tratamento precoce de doença
micrometastática
• Preditor de resposta à RT
• Alívio de sintomas relacionados
ao tumor, antes RT
• Preservação de órgão
• Estudo de biomarcadores
preditivos de resposta
Qual o papel da
QT neoadj no
HNSCC ?• Avaliar resposta tumoral in vivo
• Tratamento precoce de doença
micrometastática
• Preditor de resposta à RT
• Alívio de sintomas relacionados
ao tumor, antes RT
• Preservação de órgão
• Estudo de biomarcadores
preditivos de resposta
MACH – NC 2009
Pignon et al., 2009
PARADIGM trial
Overall Survival
P=
0.77
Progression Free
Survival
HR=1.07; 95%CI 0,59-
1,92
HR=1.09; 95%CI 0,59-
2,03
P=
0.82
Haddad et al. Lancet Oncol 2013
Desenho do estudo – Fase III
TPF* x 3Elegíveis
N= 421
• CEC
• Cavidade oral;
• orofaringe,
• hipofaringe
• EC III e IVA
• ECOG PS 0 e 1 Sem QT de indução
R
A
N
D
O
M
I
Z
A
D
O
S
RT 70Gy
PF
RT 70Gy
Cetuximabe(400 + 250mg/sem)
RT 70Gy
PF
RT 70Gy
Cetuximabe(400 + 250mg/sem)
Desfecho primário: Sobrevida global em 3 anos (indução vs não
indução)
* TPF: Docetaxel 75mg/m2 D1, CDDP 80mg/m2 D1 e 5FU 800mg/m2 D1-5/ PF: CDDP 20mg/m2 D1-4 , 5FU 800mg D1-5 sem 1 e
6.
n= 129
n= 79
n= 129
n= 78
Resultados
Sobrevida Global
201
4
Ghi MG. Abst # 6006
ESMO Guidelines
D´Souza G, et al. N Engl J Med. 2007;356(19):1944-1956
HPV Detection
Bishop JA, et al. Semin Diagn Pathol. 2015 Sep;32(5):344-51.
H&E P16 IHC
ISH for high risk HPV
DNA
ISH for E6/E7
mRNA
Optimal Testing Method for HPV?
Bishop JA, et al. Semin Diagn Pathol. 2015 Sep;32(5):344-51.
‘’It is now acknowledged that detecting transcriptionally active,
high-risk HPV is a necessity in routine clinical practice, but there is
considerable confusion among pathologists and clinicians alike
about the subsites and settings in which HPV testing should be
performed. Compounding this lack of clarity is the fact that there
are multiple HPV testing options available, but currently there is no
clear consensus on which test or combination of tests is optimal
for routine diagnostic use.’’
Ang KK, et al. N Engl J Med. 2010;363(1):24-35
RTOG 0129
HPV Survival Analyses
M. Gillison
HPV-Positivity:
Outcome Effects in RT
Ang KK, N Engl J Med. 2010;363:24-35; Rischin D, et al. J Clin Oncol. 2010;28(18):2989-2995; Beitler JJ, et al. Int J
Radiat Oncol Biol Phys. 2014;89(1):13-20; Posner MR, et al. Ann Oncol. 2011;22(5):1071-1077
TAX 324TPF vs PF Induction in
Locally Advanced HNSCC
Posner MR, et al. Ann Oncol. 2011;22(5):1071-1077
Vermorken JB, et al. Lancet Oncol.
2013;14(8):697-710
SPECTRUMCisplatin + Flurouracil ± Panitumumab
Oral HPV DNA Detection
Rettig E, et al. J Clin Oncol. 2015;33(Suppl): Abstract 6005
Time HPV16 prevalence,
N(%)
Other high-risk HPV
prevalance, N (%)
Diagnosis 67 (54%) 27 (22%)
Post-treatment 6 (5%) 17 (14%)
Persistent 5 (4%) 7 (6%)
Newly detected 1 (1%) 12 (10%)
% Cleared post-
treatment
93% 74%
Persistent Oral HPV16 DNA Detection
is Associated With Poor Survival
Rettig E, et al. J Clin Oncol. 2015;33(Suppl): Abstract 6005
5 participants with
persistent oral
HPV16
• All (5/5) recurred
• Most (3/5) died
of disease